1. Field of the Invention
This invention is directed to preparation of 3-isothiazolone compounds.
2. Description of the Prior Art
3-Isothiazolone compounds are highly effective microbicides and have generated much commercial interest to prevent spoilage of certain aqueous and non-aqueous products caused by microorganisms.
An especially commercially important 3-isothiazolone biocide is a mixture of 5-chloro-2-methyl-3-isothiazolone (CMI) and 2-methyl-3-isothiazolone (MI). All known processes to produce either of these compounds results in a mixture of the two. Therefore, in order to obtain either one essentially free of the other, the mixtures require separation. Until the present invention, this was both difficult and expensive.
U.S. Pat. No. 5,028,620 discloses preparing substantially pure MI by recrystallization of a crude MI.hydrochloride (HCl) salt followed by neutralization, and substantially pure CMI by partial neutralization, with pyridine, of a mixture of MI.HCl and CMI.HCl. U.S. Pat. No. 5,068,344 discloses preparing mostly pure CMI by partial neutralization of a mixture of MI.HCl and CMI.HCl with ammonia gas.
The methods taught in these U.S. patents for partially neutralizing the isothiazolone.HCl salt mixtures require the handling of an additional component (pyridine or ammonia) and provide CMI with a small amount of MI. Substantially pure MI must be obtained by other means (such as by recrystallization of the hydrochloride salt followed by neutralization).
Conventional methods of preparing the mixture of salts include, for example, cyclizing N,N'-dimethyl-3,3'-dithiopropionamide or N-methyl-3-mercaptopropionamide with a halogenating agent. The mixture of salts precipitates from the reaction mixture and can be isolated by filtration. Once isolated, the isothiazolone.HCl salts are generally washed before proceeding further. Normally, the washed mixture of CMI.HCl and MI.HCl is then neutralized with a base.
Typical halogenating agents are chlorine, sulfuryl chloride, N-chlorosuccinimide, and the like. Chlorine and sulfuryl chloride are the preferred halogenating agents.
The halogenation-cyclization is conducted in an organic solvent, typically aromatic hydrocarbons, aliphatic hydrocarbons, chlorinated aliphatic hydrocarbons, acetate esters, glycol ethers and glycol ether acetates. The preferred solvents are toluene, monochlorobenzene, ethyl acetate, ethylene dichloride, and butyl acetate.
It is well known in the art that the ratio of CMI. HCl to MI.HCl in the mixture can be varied between 4.5 and 0.02 by changing the cyclization conditions, the ratios of reactants used, and the rates of addition of the reactants.
Japanese Kokai Hei 3-095103 discloses a method of preparing a mixture of CMI and MI free of certain undesirable reaction by-products by heating a mixture of the 3-isothiazolone.HCl salts to dissociate said salts and to obtain the mixture of free base CMI and MI, rather than neutralizing with a base. This Kokai does not disclose a method for separating the individual isothiazolones.